1. Field of the Invention
The present invention relates to compositions and methods for the treatment of peripheral neural and vascular ailments. In the methods of the present invention, a flavonoid is administered to a patient suffering from a peripheral neural or vascular ailment.
2. Brief Description of the Prior Art
The phrases “peripheral neuropathies” and “small fiber neuropathies” are used interchangeably herein to refer to a set of conditions characterized by functional changes or pathological changes, or both, in the small, unmyelinated nerve fibers of the peripheral nervous system.
Peripheral or small fiber neuropathies may be caused by any of about a hundred identified factors that can produce nerve damage. The cause may be metabolic, for example hypertriglyceridemia or pellagra. Toxic exposures may also cause small fiber neuropathies, for example those resulting from alcoholism, excessive doses of vitamin B6, exposure to toxic metals such as thallium, or exposure to certain chemotherapeutic agents, such as vinca alkaloids. Certain congenital conditions, including amyloidosis, an-α-lipoproteinemia (Tangier's), and α-galactosidase (Fabry's), are known to cause small fiber neuropathies. Small fiber neuropathies may result from infections such as leprosy, or diseases such as AIDS, herpes simplex, herpes zoster (shingles), cytomegalovirus, hepatitis B and C, Lyme disease, autoimmune diseases, Fabry disease, diphtheria, vasculitis, and porphyria. In approximately 15% of cases, the cause of the small fiber neuropathy cannot be determined. The neuropathy is then referred to as idiopathic.
Patients afflicted with peripheral neuropathies have pain in their extremities. The pain may at first be perceived as a tingling sensation in the fingers or toes. Decreased sensitivity to heat or cold is also a common early symptom. Frequently, however, a physical examination will show that the patient's reflexes, strength, sensory levels, and electrophysiology are normal. This has historically complicated the diagnosis of peripheral neuropathies, or led to underdiagnosis, especially in the early stages of the neuropathies. Recent technology, however, including skin biopsies and measurement of the density of different nerve fiber types in the epidermis, has improved the likelihood of detecting peripheral neuropathies.
Small fiber or peripheral neuropathies tend to progress by spreading upward, and patients may develop intense pain and/or a burning sensation that can be so severe as to be debilitating. Other symptoms of these neuropathies include cold hands or feet, cramps, muscle weakness and/or atrophy, eventual loss of perception of pressure, pain and/or temperature, neuropathic ulcers, lack of sweating, dry eyes, dry mouth, impotence, and restless leg syndrome.
In some cases, treatment of the underlying cause may also reverse or alleviate small fiber neuropathies. When the underlying cause is unidentifiable or otherwise untreatable, however, treatment consists of reducing the symptoms of the neuropathies, typically by administering medications known to decrease pain from neuropathy and related conditions. These medications include tricyclic antidepressants, anticonvulsants, opioid medications, and local anesthetics applied to the painful area. An afflicted patient may also undergo physical and occupational therapy to improve mobility and function.
Often, the symptoms of peripheral neuropathies do not vary due to their underlying causes. For example, diabetic neuropathy, a type of peripheral neuropathy, is a fairly common long-term complication of diabetes mellitus that shares many of the symptoms of peripheral neuropathies and is, therefore, included among the peripheral neuropathies as defined herein. The cause of diabetic neuropathy, however, is believed to be a chronic systemic excess of the glucose metabolite sorbitol. Further, treating the underlying cause of diabetic neuropathy, that is, improving glycemic control, will often prevent the symptoms from worsening. Diabetic neuropathy is also known to be reversible, if good glycemic control is instituted while the condition is in its early stages.
Peripheral Neuropathies, including diabetic neuropathies, can also impair circulation in the affected area. Impaired circulation can adversely affect the appearance of the skin. Adverse effects on the appearance of the skin caused by radiation injury can include, for example, redness, discoloration, dryness of the skin.
“Peripheral vascular diseases” are diseases of the blood vessels outside the heart that lead to restriction or blockage of the blood vessels. Atherosclerosis, when it affects the extremities rather than the coronary arteries, is an example of a peripheral vascular disease. Peripheral vascular diseases may also be long-term complications of other diseases, such as Raynaud's disease, Raynaud's phenomenon, hypertension, or Buerger's disease (thromboangitis obliterans).
An early symptom of peripheral vascular disease includes pain upon exercising that is relieved by rest. These diseases are progressive, however, and patients may also experience numbness, muscle weakness or pain, loss of hair on the affected extremities, cyanosis, weak or absent pulse in the affected extremities, gait abnormalities, pain when resting, skin ulcers, and, eventually gangrene. Impaired circulation caused by peripheral vascular disease can also adversely affect the appearance of the skin. Adverse effects on the appearance of the skin caused by radiation injury can include, for example, redness, discoloration, dryness of the skin.
In general, an agent that promotes or induces angiogenesis, or one that at least partially clears blocked or restricted vessels, or one that will facilitate peripheral circulation by other means, i.e. by decreasing cellular adhesion, will be effective to treat peripheral vascular diseases.
Decreased microcirculation is also a long-term complication of diabetes. In general, a therapy that is effective for peripheral vascular diseases will also be effective to counter decreased microcirculation caused by diabetes.
There remains a need for a treatment for small fiber neuropathies that is clinically effective when the underlying cause of the neuropathy is unknown. A need also remains for an effective treatment for small fiber neuropathies that does not suffer from the disadvantage of causing severe side effects.
In addition, there remains a need for a clinically effective treatment of peripheral vascular ailments.
Accordingly, it is an object of certain embodiments of the present invention to provide a method that is effective for the treatment of small fiber neuropathies and peripheral vascular ailments.
It is another object of certain embodiments of the present invention to provide a method for the treatment of small fiber neuropathies or peripheral vascular ailments by administering a composition that does not cause severe side effects in the patient.
It is another object of certain embodiments of the present invention to provide a composition for the treatment of peripheral neuropathies or peripheral vascular ailments.
These and other objects of the present invention will be apparent from the summary and detailed descriptions of the invention that follow.